With few exceptions, carcinogens are mutagenic agents that react with and damage DNA. Various physical and chemical agents are known to induce cancer in humans, such as UV-irradiation and vinyl chloride. About 80% of all human cancer is caused by environmental chemical substances, both man-made and naturally occurring. The screening of such substances for mutagenic activity and subsequent evaluation of the data could lead to greater control over the use of potentially hazardous agents, and the majority of human cancers could thereby be prevented or their incidence reduced. Animal carcinogenicity studies are not only costly but are also time consuming. In recent years a number of short-term microbial mutagenesis assays have been developed for the detection of chemical mutagens. These assays are particularly well suited for screening large numbers of chemicals. The most widely used and probably the most reliable microbial mutagenesis test is the Salmonella/mammalian-microsome reverse mutation assay. The test was significantly improved by the introduction of plasmid pKM101 in some of the tester strains. However, the test still does not detect certain classes of potent human carcinogens. The objective of the proposed research is to screen a large number of plasmids to find ones that will be superior to pKM101 or that will supplement pKM101 by making one or more tester strains responsive to known or suspected carcinogens not detected by the test in its present form. Making the test more sensitive will enhance its predictive value for human carcinogenicity induced by environmental mutagens.